TELOMERE LENGTH, TELOMERASE ACTIVITY AND TELOMERASE RNA EXPRESSION DURING MOUSE MAMMARY-TUMOR PROGRESSION

To investigate the roles of telomere length (mean length of the termin al restriction fragments; TRFs), telomerase activity (TA) and telomera se RNA (mTR) expression in relation to mouse mammary tumor progression , we examined a pregnancy-dependent mouse mammary tumor line (TPDMT-4) and its four autonomous sublines (T4-OI320: non-metastatic; and T4-OI 165, -OI96, and -OI145: artificial metastatic) of DDD/1 mouse origin, and an autonomous growing mammary tumor (JYG-MC) showing spontaneous l ung metastasis developed in BALB/c mice infected with a Chinese feral mice (Sub-Jyg)-derived mouse mammary tumor virus (JYG-MTV). Compared w ith normal (pregnant) mammary tissue, the TA was elevated in the TPDMT -4 tumor and in the non-metastatic subline tumor (T4-OI320) (x10 fold, respectively), and was further increased (x13-15 fold) in parallel wi th the acquisition of metastatic potential (T4-OI165, -OI96, and -OI14 5). The mTR level was up-regulated (x2.7-2.8 fold) in all autonomous g rowing tumors compared to the normal counter-part, but not in TPDMT-4. The TRF was shorter in accord with turner progression (normal mammary tissue, 48 kb; TPDMT-4, 45 kb; T4-OI320, 37 kb; T4-OI165, -OI96 and - OI145, mean 37.7 kb; and JYG-MC, 21 kb). These results suggest that th e activation of TA occurs as an early event at the stage of hormone-de pendent tumorigenesis, followed by the up-regulation of mTR expression in accordance with the acquisition of autonomous growth, and then fur ther activation of TA occurs when the tumor acquires metastatic potent ial. The TRF shortening was in parallel with the tumor progression.